Lanthanide Complexes of DO3A-(Dibenzylamino)methylphosphinate: Effect of Protonation of the Dibenzylamino Group on the Water-Exchange Rate and the Binding of Human Serum Albumin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10394078" target="_blank" >RIV/00216208:11310/19:10394078 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=yx8l08pQ-9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=yx8l08pQ-9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.inorgchem.9b00267" target="_blank" >10.1021/acs.inorgchem.9b00267</a>
Alternative languages
Result language
angličtina
Original language name
Lanthanide Complexes of DO3A-(Dibenzylamino)methylphosphinate: Effect of Protonation of the Dibenzylamino Group on the Water-Exchange Rate and the Binding of Human Serum Albumin
Original language description
Protonation of a distant, noncoordinated group of metal-based magnetic resonance imaging contrast agents potentially changes their relaxivity. The effect of a positive charge of the drug on the human serum albumin (HSA)-drug interaction remains poorly understood as well. Accordingly, a (dibenzylamino)methylphosphinate derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was efficiently synthesized using pyridine as the solvent for a Mannich-type reaction of tBu(3)DO3A, formaldehyde, and Bn2NCH2PO2H2 ethyl ester. The ligand protonation and metal ion (Gd3+, Cu2+, and Zn2+) stability constants were similar to those of the parent DOTA, whereas the basicity of the side-chain amino group of the complexes (logK(A) = 5.8) was 1 order of magnitude lower than that of the free ligand (log K-A = 6.8). The presence of one bound water molecule in both deprotonated and protonated forms of the gadolinium(III) complex was deduced from the solid-state X-ray diffraction data [gadolinium(III) and dysprosium(III)], from the square antiprism/twisted square antiprism (SA/TSA) isomer ratio along the lanthanide series, from the fluorescence data of the europium(III) complex, and from the O-17 NMR measurements of the dysprosium(III) and gadolinium(III) complexes. In the gadolinium(III) complex with the deprotonated amino group, water exchange is extremely fast (tau(M) = 6 ns at 25 degrees C), most likely thanks to the high abundance of the TSA isomer and to the presence of a proximate protonable group, which assists the water-exchange process. The interaction between lanthanide(III) complexes and HSA is pH-dependent, and the deprotonated form is bound much more efficaciously (similar to 13% and similar to 70% bound complex at pH = 4 and 7, respectively). The relaxivities of the complex and its HSA adduct are also pH-dependent, and the latter is approximately 2-3 times increased at pH = 4-7. The relaxivity for the supramolecular HSA-complex adduct (r(1)(b)) is as high as 52 mM(-1) s(-1) at neutral pH (at 20 MHz and 25 degrees C). The findings of this study stand as a proof-of-concept, showing the ability to manipulate an albumin-drug interaction, and thus the blood pool residence time of the drug, by introducing a positive charge in a side-chain amino group.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10402 - Inorganic and nuclear chemistry
Result continuities
Project
<a href="/en/project/LTC17067" target="_blank" >LTC17067: Application of NMR relaxation and diffusion measurements to assess dynamics of complex molecular systems</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganic Chemistry
ISSN
0020-1669
e-ISSN
—
Volume of the periodical
58
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
5196-5210
UT code for WoS article
000465188700052
EID of the result in the Scopus database
2-s2.0-85064438849